The clinical relevance of HLA-G in cancer is supported by the following observations: (i) HLA-G expression is associated with malignant transformation and is never observed in healthy surrounding tissues [5]; (ii) HLA-G is found to be expressed in solid tumors of high histological grades and advanced clinical stages [6, 7]; and (iii) the use of HLA-G as a prognostic marker has been proposed since HLA-G expression in biopsies and/or high levels of soluble HLA-G (sHLA-G) in plasma from patients have been significantly correlated with poor prognosis [6–11]. The gene discussed is HLA-G; the disease is cancer.